Project Summary The overarching objective of the proposed research is to develop and explore the mode of operation of a novel family of first-row transition-metal reagents for the amination of unfunctionalized hydrocarbons. The proposed reagents deliver nitrogen groups (nitrenes, amidos, nitrenoids) to aliphatic hydrocarbons (C?H bonds) and olefins (C=C bonds) for the construction of C?N bonds. Sites of amination are present in a plethora of natural and synthetic products, including pharmaceuticals, agrochemicals, catalytic agents and solid-state materials, in order to confer backbone characteristics and specific functionalities necessary for activity. The principal objective will be accomplished via three specific aims, accomplished in a parallel and mutually informed fashion. First, a novel library of stereo-electronically diverse ligand scaffolds will be synthesized and used as a robust framework to anchor metal sites, producing divalent iron, manganese, cobalt, and monovalent copper reagents, functioning as catalysts for amination reactions. Secondly, the metal reagents will be explored as catalysts for the transfer of nitrogen groups (nitrenes, amidos, nitrenoids) from suitable precursors to versatile carbonaceous substrate acceptors (alkanes, alkenes), leading to the formation of important functional units (amines, diamines, unprotected aziridines). Stoichiometric reactions involving the metal reagents and the nitrogen-group sources (in the absence of substrates) will be conducted to identify critical metal-centered intermediates responsible for delivering the nitrogen group to the substrate. Thirdly, the most promising reagents will be mechanistically investigated, to report on the mode of transfer and subsequent insertion/addition of the nitrogen group unit to the substrate, and further guide catalyst development for efficient and selective aminations. The proposed work relies on the availability of a library of house-made novel metal reagents, featuring members with a proven record in C?N bond construction, but requiring expansion to achieve appropriate levels of selectivity in the synthesis of a wider range of amination products. Moreover, the proposed research explores reactivity patterns that may share common characteristics in catalysis and enzymology, to indirectly address mechanistic questions arising from emerging classes of enzymes involved in amination reactions. The eventual outcome of the proposed activities is to introduce novel reagents in the arsenal of the synthetic chemist, deriving from the abundant first-row transition elements, and aspiring to surpass or complement current C?N bond construction methodologies in terms of scope, selectivity, and mechanistic insight.